This proposal will test the hypothesis of bidirectional positive feedback at the central chemoreceptors for ventilatory control. We propose that activation of a group of neurons near the central chemoreceptors such as the ventral respiratory group can increase local metabolism, cause the elaboration of acid metabolites and thereby stimulate the central chemosensitive cells. Such a mechanism would constitute a positive feedback loop in the respiratory control system and could explain phenomena such as isocapnic hyperpnea associated with hypermetabolism. In addition, a positve feedback loop of this nature could be bidirectional since an increase in local blood flow in excess of metabolism would reduce the extracellular [H+] resulting in a diminuation of respiratory drive. This proposal concerns itself with the investigation of this hypothesis of bidirectional positive feedback in respiratory control using autoradiographic and microelectrode techniques. In cats we propose to determine the relationships of ventral medullary blood flow (iodo-14C-antipyrine method) and metabolism (2 deoxy-14C-glucose method), as well as the pH in the ventral medulla (microelectrodes) during two situations of increased respiratory drive without associated blood gas changes: (a) carotid sinus nerve stimulation in a paralyzed artificially ventilated animal; and (b) simulated exercise. Secondly, we will measure ventral medullary blood flow during two situations of decreased respiratory drive which we postulate to be the result of a descreased extracellular [H+] consequential to excess perfusion: (a) hypoxia in peripherally chemodenervated cats; and (b) REM sleep. Should the hypothesis prove correct, it will enhance understanding of heretofore obscure phenomena such as isocapnic hyperpnea, depression of ventilation due to CNS hypoxia and breathing irregularities during REM sleep.